Abstract
The use of antisense oligonucleotides (AONs) is a promising therapeutic strategy for central nervous system disorders. However, the delivery of AONs to the central nervous system is challenging because their size does not allow them to diffuse over the blood-brain barrier (BBB) when injected systemically. The BBB can be bypassed by administering directly into the brain. Here we describe a method to perform single and repeated intracerebroventricular injections into the lateral ventricle of the mouse brain.
Highlights
There has been a recent revival of interest in the use of antisense oligonucleotides (AONs) to treat neurodegenerative disorders with one approved central nervous system AON therapy and several in clinical trials [1]
This is largely due to the remarkably widespread distribution and cellular uptake of AONs once delivered into the brain
The blood–brain barrier (BBB) is bypassed by injecting the AON directly into the lateral ventricle, after which the AONs pass the ependymal cell layer that lines the ventricular system and enters the brain parenchyma
Summary
There has been a recent revival of interest in the use of antisense oligonucleotides (AONs) to treat neurodegenerative disorders with one approved central nervous system AON therapy and several in clinical trials [1]. This is largely due to the remarkably widespread distribution and cellular uptake of AONs once delivered into the brain. Since the molecular weight of AONs is approximately 6000–10,000 Da, they are too large to cross the BBB by simple diffusion when delivered systemically. Repeated injections of AONs lead to a widespread distribution throughout the entire mouse brain, and the protein modifying effect can be detected in the cortex, cerebellum, and brainstem [6]. We describe a method for ICV delivery of AONs through a single injection or repeated injections using a cannula (Fig. 1)
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